Alpha-1-antitrypsin is the major proteinase inhibitor in human sera. The most common form of this glycoprotein (i.e., the homozygote MM phenotype), as well as the homozygote ZZ phenotype which is associated with chronic obstructive lung disease have been purified using classical chromatographic procedures. For the Z protein, special precautions to prevent aggregation including the use of mercaptoethanol, and the elimination of dialysis and freeze-drying procedures are required. The purified proteins will be compared by a variety of biological, immunological and conformational parameters. In addition, each purified phenotypic protein exhibits a characteristic pattern of protein bands on a discontinuous acid starch gel electrophoresis. The major bands will be separated by isoelectric focusing. Variant peptides derived from the purified proteins after enzymic digestion will be compared after peptide mapping or column chromatography procedures by peptide sequencing. Carbohydrate containing peptides will be isolated by specific absorption on insolubilized Concanavalin A and by more conventional procedures. These studies are designed to establish the conformational and structural differences between proteins of the same phenotype as well as differences arising from genetic factors (i.e., between phenotypes).